The gene map of the domestic cat (Felis catus) has been constructed as a physical map of over 100 coding gene loci homologous to the human genes. The present map has been expanded to over 100 loci, including approximately 50 proto-oncogene loci, using a previously developed panel of cell hybrids. These markers have been used to define the syntenic segments of primitive chromosome associations between the human and feline genetic maps. Interspecies crosses between F. catus and leopard cat Prionailurus bengalensis and between F. catus and Leopardus geoffroyi have been initiated in order to produce backcross offspring to define a linkage map of domestic cat. To date, over 50 interspecies hybrid offspring have been born following artificial insemination; of these, 12 healthy females are maturing. Methods for in situ hybridization of feline metaphase chromosomes using biotin-labeled molecular clones have been attempted and improved. Procedures using human chromosome libraries for chromosome "painting," i.e., visualization of homologous chromosome segments between carnivores and primates, are in progress. To date nearly 35% of the human genome can be aligned band-for-band with chromosome segments of the cat genome. The combination of the three present methods (hybrid panel, heterologous species crosses, and chromosome painting) holds much promise in reconstruction of the historic phylogenetic genome exchanges.